Human Molecular Genetics, Vol 5, 257-263, Copyright © 1996 by Oxford University Press
E Velasco, C Valero, A Valero, F Moreno and C Hernandez-Chico
Spinal muscular atrophy is an autosomal recessive disorder which affects
about 1 in 10,000 individuals. The three clinical forms of SMA were mapped
to the 5q13 region. Three candidate genes have been isolated and shown to
be deleted in SMA patients: the Survival Motor Neuron gene (SMN), the
Neuronal Apoptosis Inhibitory Protein gene (NAIP) and the XS2G3 cDNA. In
this report we present the molecular analysis of the SMN exons 7 and 8 and
NAIP exon 5 in 65 Spanish SMA families. NAIP was mostly deleted in type I
patients (67.9%) and SMN was deleted in 92.3% of patients with severe and
milder forms. Most patients who lacked the NAIP gene also lacked the SMN
gene, but we identified one type II patient deleted for NAIP exon 5 but not
for SMN exons 7 and 8. Two other patients carried deletions of NAIP exon 5
and SMN exon 7 but retained the SMN exon 8. Three polymorphic variants from
the SMN gene, showing changes on the sequence of the centromeric (cBCD541)
and telomeric copies of the SMN gene, were found. In addition, we show
several genetic rearrangements of the telomeric SMN gene, which include
duplication of this gene in one normal chromosome, and putative gene
conversion events in affected and normal chromosomes. Altogether these
results corroborate the high genetic variability of the SMA region.
Finally, we have determined the ratio between the number of centromeric and
telomeric copies of the SMN gene in parents of SMA patients, showing that
the majority of parents of types II and III patients carried three or more
copies of the cBCD541 gene; we suggest a relationship between the number of
copies of cBCD541 and the disease phenotype.
ARTICLES
Molecular analysis of the SMN and NAIP genes in Spanish spinal muscular atrophy (SMA) families and correlation between number of copies of cBCD541 and SMA phenotype [published erratum appears in Hum Mol Genet 1996 May;5(5):710]
Unidad de Genetica Molecular, Hospital Ramon y Cajal, Madrid, Spain.
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